Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention

Abstract

The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae.

Keywords::

• Gel
• drug delivery
• antiviral
• HSV
• lactobacilli
• efficacy
• safety

Acknowledgments

We are grateful for the significant contributions of Roger Schnaare toward editing of this manuscript. Additionally we would like to acknowledge Frank Sorgi (currently at DPT Laboratories, Ltd. San Antonio, TX) and Hans Hofland (currently at Stiefel Laboratories, Inc. North Carolina) who were previously at Optime for their contributions to liposome product manufacture and hydrolysis assessment. Finally, we would like to acknowledge the grant support provided by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institute of Health (5 P01 Transport and Activity of Microbicide Formulations, A139061, Principle Investigator: Hillier, Sharon, Magee Womens Research Institute) and the grant support by Public Health Services (WaNPRC RR00166). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Declaration of interest

Grant support was provided by the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institute of Health (5 P01 Transport and Activity of Microbicide Formulations, A139061, Principle Investigator: Hillier, Sharon, Magee Womens Research Institute) and Public Health Services (WaNPRC RR00166). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.